Convection-Enhanced Delivery of 124I-8H9 for Patients With Non-Progressive Diffuse Pontine Gliomas Previously Treated With External Beam Radiation Therapy - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborators:	Weill Medical College of Cornell University Johns Hopkins University School of Medicine (Data analysis only)
Information provided by (Responsible Party):	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01502917

Purpose

The purpose of this study is to test the safety of a new method to treat Diffuse Intrinsic Pontine Glioma (DIPG). The researchers will use "convection-enhanced delivery" (CED) to deliver an agent called 124I-8H9. CED is performed during surgery. The study agent is infused through a small tube placed into the tumor in the brain. Many studies have shown this can safely be done in animals but this study is the first time 124I-8H9 will be given by CED in humans. This will be one of the first times that CED has been performed in the brain stem.

8H9 is something called an antibody. Antibodies are made by the body to fight infections and sometimes cancer. The antibody 8H9 is produced by mice and can attack many kinds of tumors. A radioactive substance, 124I, is attached to 8H9. 124I-8H9 sticks to parts of tumor cells and can cause the tumor cells to die from radiation. Studies have also been done on humans using 124I-8H9 to treat other kinds of cancer. Our studies of some DPG and related tumors suggest that 8H9 will bind to the tumor, but the investigators don't know that for sure.

In this study, the researchers want to find out how safe 124I-8H9 given by CED is at different dose levels. They will look to see what effects (both good and bad) it has on the patient. The dose of 124I-8H9 will increase for each new group of patients. The amount they get will depend on when they enter the study. If too many serious side effects are seen with a certain dose, no one will be treated with a higher dose, and some more patients may be treated with a lower dose to make sure that dose is safe.

Condition	Intervention	Phase
Brain Cancer Brain Stem Glioma	Radiation: Radioactive iodine-labeled monoclonal antibody 8H9	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Study of Convection-Enhanced Delivery of 124I-8H9 for Patients With Non-Progressive Diffuse Pontine Gliomas Previously Treated With External Beam Radiation Therapy

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer Childhood Brain Tumors

Drug Information available for: Iodine Iodide

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

maximum tolerated dose [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Determination that a dose is safe will be made following the treatment of at least 3 but no more than 6 patients at a particular dose level. The dose levels are DL1 (0.25 mCi), DL2 (0.5 mCi), DL3 (0.75 mCi), DL4 (1 mCi) and fallback DL0 (0.125 mCi). An incidence of dose-limiting toxicity (DLT) in the range of 25% is considered acceptable in this population.
safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Adverse events (toxicity) will be assessed and classified by the Clinical Terminology Criteria for Adverse Events version 4.0 (CTCAE). Generally, grade 3 toxicities interfere with activities of daily living (ADLs) and grade 4 toxicities are life-threatening. Grade 5 toxicities cause death.

Secondary Outcome Measures:

overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Overall survival from the time of diagnosis will be recorded for every patient in this study. Overall survival will be estimated by Kaplan-Meier methodology.

Estimated Enrollment:	12
Study Start Date:	December 2011
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Radioactive iodine-labeled monoclonal antibody 8H9 This is a therapeutic Phase I study intended to assess the safety of convection-enhanced delivery (CED) of radioimmunotherapy in the treatment of children with diffuse pontine glioma.	Radiation: Radioactive iodine-labeled monoclonal antibody 8H9 Each patient is planned to undergo stereotactic placement of an infusion cannula. Through this cannula, CED of 124I-8H9 at a rate of ≤ 10 μl/min will be performed. Infusion doses of 124I-8H9 will be incrementally increased in subsequent groups of patients to test for safety of the procedure and therapeutic agent (0.25, 0.5, 0.75 and 1 mCi). They will be monitored for a minimum of one night in the pediatric ICU after the completion of the infusion. They will then be transferred to the standard pediatric inpatient ward for observation and discharged once deemed appropriate by the principal or co-investigators. PET/CT scans will be performed following surgery to document both radiographic change and infusate distribution in tumor as well as to provide the time-activity data needed for radiation dosimetry analysis. PET/CT will be performed of the entire body, low mA will be used. These images will be co-registered to MRIs previously performed to accurately describe radiation distribution. Other Names: After discharge follow-up will be as follows: will be seen on a weekly basis post-operatively for 1 month during which detailed neuro exam will be performed. At about 2 weeks following surg suture removal & blood work (cbc, comprehensive metabolic panel, & PT/PTT) will be performed. The patient will then be clinically evaluated with detailed neurological examination again about 30 days following infusion to evaluate for any delayed toxicity. This evaluation will also include blood work (complete blood count, comprehensive metabolic panel, and PT/PTT). After the 30-day evaluation, the patient will be seen monthly until disease progression or up to two (2) years followed as any patient with a diffuse pontine glioma by oncologic caregivers. During these visits, objective neurological examination and Karnofsky score should be documented. HAMA testing will be performed after 2 weeks, one month and every 3 months thereafter up to two (2) years.

Arms

Assigned Interventions

Experimental: Radioactive iodine-labeled monoclonal antibody 8H9

This is a therapeutic Phase I study intended to assess the safety of convection-enhanced delivery (CED) of radioimmunotherapy in the treatment of children with diffuse pontine glioma.

Radiation: Radioactive iodine-labeled monoclonal antibody 8H9

Each patient is planned to undergo stereotactic placement of an infusion cannula. Through this cannula, CED of 124I-8H9 at a rate of ≤ 10 μl/min will be performed. Infusion doses of 124I-8H9 will be incrementally increased in subsequent groups of patients to test for safety of the procedure and therapeutic agent (0.25, 0.5, 0.75 and 1 mCi). They will be monitored for a minimum of one night in the pediatric ICU after the completion of the infusion. They will then be transferred to the standard pediatric inpatient ward for observation and discharged once deemed appropriate by the principal or co-investigators. PET/CT scans will be performed following surgery to document both radiographic change and infusate distribution in tumor as well as to provide the time-activity data needed for radiation dosimetry analysis. PET/CT will be performed of the entire body, low mA will be used. These images will be co-registered to MRIs previously performed to accurately describe radiation distribution.

Other Names:

After discharge follow-up will be as follows: will be seen on a weekly basis
post-operatively for 1 month during which detailed neuro exam will be performed.
At about 2 weeks following surg suture removal & blood work (cbc, comprehensive
metabolic panel, & PT/PTT) will be performed. The patient will then be clinically evaluated with detailed neurological examination again about 30 days
following infusion to evaluate for any delayed toxicity. This evaluation will
also include blood work (complete blood count, comprehensive metabolic panel,
and PT/PTT). After the 30-day evaluation, the patient will be seen monthly until
disease progression or up to two (2) years followed as any patient with a
diffuse pontine glioma by oncologic caregivers. During these visits,
objective neurological examination and Karnofsky score should be documented.
HAMA testing will be performed after 2 weeks, one month and every 3 months
thereafter up to two (2) years.

Eligibility

Ages Eligible for Study:	3 Years to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Consensus of diagnosis must be reached by a multidisciplinary pediatric neuro-oncology team by considering both clinical evidence and MRI presentation. Tissue diagnosis is not required.
The patient must have undergone prior external beam radiotherapy to a dose of 54-60 Gy to the brain stem. At least 4 weeks but no more than 14 weeks must have elapsed from the completion of radiotherapy.
The patient must be in adequate general condition for study, with Lansky or Karnofsky Performance Score > or = to 50 at study entry .

Lansky Performance scale will be used for patients ≤16 years of age.

The patient must be > to or = to 3 and ≤ 21 years old.
Patient must weigh a minimum of 8 kg.

Exclusion Criteria:

Clinical and/or radiographic (MRI) progression of tumor following external beam radiation therapy.
Metastatic disease.
Untreated symptomatic hydrocephalus determined by treating physician.
AST or ALT > 2x the upper limit of normal.
Platelets < 100,000.
ANC < 1000.
Abnormal PT/INR or PTT (may be corrected with FFP, cryoprecipitate, vitamin K, etc).
Total bilirubin > 2.0 mg/dl.
Serum creatinine > 1.5x the upper limit of normal for age, or calculated creatinine clearance or nuclear GFR < 70 ml/min/1.73 m2.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01502917

Contacts

Contact: Mark Souweidane, MD	212-639-2336
Contact: Ira Dunkel, MD	212-639-2336

Locations

United States, New York
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Kim Springer 212-639-2336
Principal Investigator: Mark Souweidane, MD
Weill Medical College of Cornell University	Not yet recruiting
New York, New York, United States, 10021
Contact: Kim Springer 212-639-2336

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Weill Medical College of Cornell University

Johns Hopkins University School of Medicine (Data analysis only)

Investigators

Principal Investigator:

Mark Souweidane, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01502917 History of Changes
Other Study ID Numbers:	11-011
Study First Received:	December 29, 2011
Last Updated:	March 19, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Brain stem glioma
CNS
MAB 124I-8H9
infusion cannula

DIPG
Diffuse Intrinsic Pontine Glioma
11-011

Additional relevant MeSH terms:

Brain Neoplasms
Glioma
Pontine Glioma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue
Astrocytoma
Antibodies
Antibodies, Monoclonal
Iodine
N-(2-aminoethyl)-5-isoquinolinesulfonamide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Trace Elements
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on May 23, 2012